Low excretor glutaric acidemia type 1 with transient lesions in the basal ganglia

In some countries, glutaric acidemia type 1 (GA1) is included in newborn screening (NBS) panels using tandem mass spectrometry (MS/MS) analysis of acylcarnitine. However, the low excretor phenotype of glutaric acidemia type 1 (LE-GA1) has been increasingly recognaized and may lead to false-negative NBS results and can be missed by urine organic acid and plasma acylcarnitine profile analyses.

We report a case of LE-GA1 with an atypical imaging course. NBS by dried blood spot acylcarnitine profile using MS/MS was normal. At 7 months of age, he developed an acute encephalopathic crisis with bilateral striatal lesions. He underwent intravenous methylprednisolone pulse, intravenous immunoglobulin, vitamin B1, biotin, l-carnitine, and coenzyme Q10 therapy. Abnormal basal ganglia signals disappeared within 4 weeks. Serial brain MRI 6 months later revealed linear lesions in both putamen. The plasma acylcarnitine profile and urine organic acid analyses were normal at onset. Whole exome and Sanger sequencing were performed, and compound heterozygosity for the two known pathogenic variants in the glutaryl-CoA dehydrogenase gene were identified. Metabolomic analyses of the patient's urine showed elevated glutaric acid and 3-hydroxyglutaric acid levels similar to those in another LE-GA1 case. Thus, the patient was diagnosed with LE-GA1.

Unlike classical GA1, LE-GA1 may present with variable neuroimaging courses, including transient basal ganglia lesions. If Leigh's encephalopathy-like lesions of the basal ganglia-of unknown cause with acute onset-are present, LE-GA1 should be considered. To ensure timely and accurate diagnosis, genetic analyses should be performed, even if biochemical findings are normal.